rs587777634

Variant names:

• chr20-62163555-GCAGGGCAGC-G
• rs587777634
• NM_198935.3:c.660_668delCAGCCAGGG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM4 BS2

The NM_198935.3(SS18L1):​c.660_668delCAGCCAGGG​(p.Ser221_Gly223del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000171 in 1,458,534 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: SS18L1 NM_198935.3 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.67
• Publications: 0 publications found

Genes affected

SS18L1 (HGNC:15592): (SS18L1 subunit of BAF chromatin remodeling complex) This gene encodes a calcium-responsive transactivator which is an essential subunit of a neuron-specific chromatin-remodeling complex. The structure of this gene is similar to that of the SS18 gene. Mutations in this gene are involved in amyotrophic lateral sclerosis (ALS). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

SS18L1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_198935.3.
• BS2: High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.660_668delCAGCCAGGG	p.Ser221_Gly223del	disruptive_inframe_deletion	Exon 6 of 11	ENST00000331758.8	NP_945173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8	c.660_668delCAGCCAGGG	p.Ser221_Gly223del	disruptive_inframe_deletion	Exon 6 of 11	1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000370848.8	c.414_422delCAGCCAGGG	p.Ser139_Gly141del	disruptive_inframe_deletion	Exon 3 of 9	1		ENSP00000359885.5
SS18L1	ENST00000492466.2	n.102_110delCAGCCAGGG		non_coding_transcript_exon_variant	Exon 1 of 7	5		ENSP00000434451.2
SS18L1	ENST00000491916.1	n.*27_*35delCAGGGCAGC		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000822 AC: 2 AN: 243378 AF XY: 0.00000752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000917

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1458534 Hom.: 0 AF XY: 0.0000207 AC XY: 15 AN XY: 725654

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000448 AC: 2 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111714

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Mar 02, 2023

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7
Mutation Taster		=27/173	disease causing (fs/PTC)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587777634; hg19: chr20-60738611;